Mice presenting a schizophrenia-like phenotype show alterations in maturation of perineuronal nets.

CARLOS A. PRETELL ANNAN; JUAN E. BELFORTE

Mar del Plata

Congreso; XXXII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2017

Sociedad Argentina de Investigación en Neurociencias

Although the etiology of schizophrenia is not known, cortical GABAergic interneurons expressing the calcium-binding protein parvalbumin (PVs) have been implicated in its pathophysiology: levels of GAD67 and PV have consistently been found to be decreased in human postmortem brain studies. Furthermore, perineuronal nets (PNNs) have also been shown to be diminished in brain tissue from schizophrenic patients especially in PVs. PNNs ? reticular structures of extracellular matrix that surround the soma and proximal dendrites of many neurons in the CNS, including PVs ? are reportedly involved in synapse formation and stabilization.Given that normal wiring of cortical circuits relies on the proper maturation of PVs during the postnatal period, and considering the neurodevelopmental aspect of schizophrenia, we hypothesized that an unsatisfactory formation of PNNs in early adulthood could be related to the onset of the disease. In order to address this, we resorted to an NMDA receptor knockout mouse model of schizophrenia and performed immunofluorescent stainings against PV and PNNs in young and adult mice, focusing in the medial prefrontal cortex. We found no differences in PNNs among asyntomatic pre-adolescent animals, but adult KO mice showed a greater percentage of PVs not enwrapped by PNNs when compared to adult controls. Thus, we conclude that the unsatisfactory maturation of PNNs during adolescence could be pathogenetically relevant for the emergence of the altered state.